Identification and inhibition of hydrolases in Mycobacterium tuberculosis



 DESCRIPTION (provided by applicant): One-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). The majority of these individuals have asymptomatic latent infections, which are the major reservoir for this pathogen. Also, frontline anti-TB drugs have only poor efficacy against latent TB. Therefore, identifying new drug targets for latent TB is integral to any strategy for TB eradication. The serine hydrolases represent a promising but understudied family of potential novel targets. This study will (1) profile serine hydrolase activity and (2) test the therapeutic potential of inhibiting serne hydrolases, both during active growth and non-replicating latency. We anticipate that the results of this study will aid the identification of targets important for mycobacterial survival during latency and provide therapeutic leads that can be optimized for clinical use against TB.